Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis

Background: Infections due to antibiotic-resistant bacteria are threatening modern health care. However, estimating their incidence, complications, and attributable mortality is challenging. We aimed to estimate the burden of infections caused by antibiotic-resistant bacteria of public health concern in countries of the EU and European Economic Area (EEA) in 2015, measured in number of cases, attributable deaths, and disability-adjusted life-years (DALYs). Methods: We estimated the incidence of infections with 16 antibiotic resistance–bacterium combinations from European Antimicrobial Resistance Surveillance Network (EARS-Net) 2015 data that was country-corrected for population coverage. We multiplied the number of bloodstream infections (BSIs) by a conversion factor derived from the European Centre for Disease Prevention and Control point prevalence survey of health-care-associated infections in European acute care hospitals in 2011–12 to estimate the number of non-BSIs. We developed disease outcome models for five types of infection on the basis of systematic reviews of the literature. Findings: From EARS-Net data collected between Jan 1, 2015, and Dec 31, 2015, we estimated 671 689 (95% uncertainty interval [UI] 583 148–763 966) infections with antibiotic-resistant bacteria, of which 63·5% (426 277 of 671 689) were associated with health care. These infections accounted for an estimated 33 110 (28 480–38 430) attributable deaths and 874 541 (768 837–989 068) DALYs. The burden for the EU and EEA was highest in infants (aged <1 year) and people aged 65 years or older, had increased since 2007, and was highest in Italy and Greece. Interpretation: Our results present the health burden of five types of infection with antibiotic-resistant bacteria expressed, for the first time, in DALYs. The estimated burden of infections with antibiotic-resistant bacteria in the EU and EEA is substantial compared with that of other infectious diseases, and has increased since 2007. Our burden estimates provide useful information for public health decision-makers prioritising interventions for infectious diseases

Factors contributing to intervention fidelity in a multi-site chronic disease self-management program

BACKGROUND AND OBJECTIVES: Disease self-management programs have been a popular approach to reducing morbidity and mortality from chronic disease. Replicating an evidence-based disease management program successfully requires practitioners to ensure fidelity to the original program design. METHODS: The Florida Health Literacy Study (FHLS) was conducted to investigate the implementation impact of the Pfizer, Inc. Diabetes Mellitus and Hypertension Disease Self-Management Program based on health literacy principles in 14 community health centers in Florida. The intervention components discussed include health educator recruitment and training, patient recruitment, class sessions, utilization of program materials, translation of program manuals, patient retention and follow-up, and technical assistance. RESULTS: This report describes challenges associated with achieving a balance between adaptation for cultural relevance and fidelity when implementing the health education program across clinic sites. This balance was necessary to achieve effectiveness of the disease self-management program. The FHLS program was implemented with a high degree of fidelity to the original design and used original program materials. Adaptations identified as advantageous to program participation are discussed, such as implementing alternate methods for recruiting patients and developing staff incentives for participation. CONCLUSION: Effective program implementation depends on the talent, skill and willing participation of clinic staff. Program adaptations that conserve staff time and resources and recognize their contribution can increase program effectiveness without jeopardizing its fidelity

Seascape Genetics of a Globally Distributed, Highly Mobile Marine Mammal: The Short-Beaked Common Dolphin (Genus Delphinus)

Identifying which factors shape the distribution of intraspecific genetic diversity is central in evolutionary and conservation biology. In the marine realm, the absence of obvious barriers to dispersal can make this task more difficult. Nevertheless, recent studies have provided valuable insights into which factors may be shaping genetic structure in the world's oceans. These studies were, however, generally conducted on marine organisms with larval dispersal. Here, using a seascape genetics approach, we show that marine productivity and sea surface temperature are correlated with genetic structure in a highly mobile, widely distributed marine mammal species, the short-beaked common dolphin. Isolation by distance also appears to influence population divergence over larger geographical scales (i.e. across different ocean basins). We suggest that the relationship between environmental variables and population structure may be caused by prey behaviour, which is believed to determine common dolphins' movement patterns and preferred associations with certain oceanographic conditions. Our study highlights the role of oceanography in shaping genetic structure of a highly mobile and widely distributed top marine predator. Thus, seascape genetic studies can potentially track the biological effects of ongoing climate-change at oceanographic interfaces and also inform marine reserve design in relation to the distribution and genetic connectivity of charismatic and ecologically important megafauna

Amyloid-related imaging abnormalities in the DIAN-TU-001 trial of gantenerumab and solanezumab: lessons from a trial in dominantly inherited Alzheimer disease

OBJECTIVE: To determine the characteristics of participants with amyloid-related imaging abnormalities (ARIA) in a trial of gantenerumab or solanezumab in dominantly inherited Alzheimer disease (DIAD). METHODS: 142 DIAD mutation carriers received either gantenerumab SC (n=52), solanezumab IV (n=50), or placebo (n=40). Participants underwent assessments with the Clinical Dementia Rating® (CDR®), neuropsychological testing, CSF biomarkers, β-amyloid positron emission tomography (PET), and magnetic resonance imaging (MRI) to monitor ARIA. Cross-sectional and longitudinal analyses evaluated potential ARIA-related risk factors. RESULTS: Eleven participants developed ARIA-E, including 3 with mild symptoms. No ARIA-E was reported under solanezumab while gantenerumab was associated with ARIA-E compared to placebo (OR=9.1, CI[1.2, 412.3]; p=0.021). Under gantenerumab, APOE-ɛ4 carriers were more likely to develop ARIA-E (OR=5.0, CI[1.0, 30.4]; p=0.055), as were individuals with microhemorrhage at baseline (OR=13.7, CI[1.2, 163.2]; p=0.039). No ARIA-E was observed at the initial 225mg/month gantenerumab dose, and most cases were observed at doses >675mg. At first ARIA-E occurrence, all ARIA-E participants were amyloid-PET+, 60% were CDR>0, 60% were past their estimated year to symptom onset, and 60% had also incident ARIA-H. Most ARIA-E radiologically resolved after dose adjustment and developing ARIA-E did not significantly increase odds of trial discontinuation. ARIA-E was more frequently observed in the occipital lobe (90%). ARIA-E severity was associated with age at time of ARIA-E. INTERPRETATION: In DIAD, solanezumab was not associated with ARIA. Gantenerumab dose over 225mg increased ARIA-E risk, with additional risk for individuals APOE-ɛ4(+) or with microhemorrhage. ARIA-E was reversible on MRI in most cases, generally asymptomatic, without additional risk for trial discontinuation. This article is protected by copyright. All rights reserved

The association between balance and free-living physical activity in an older community-dwelling adult population: a systematic review and meta-analysis

Abstract Background Poor balance is associated with an increased risk of falling, disability and death in older populations. To better inform policies and help reduce the human and economic cost of falls, this novel review explores the effects of free-living physical activity on balance in older (50 years and over) healthy community-dwelling adults. Methods Search methods: CENTRAL, Bone, Joint and Muscle Trauma Group Specialised register and CDSR in the Cochrane Library, MEDLINE, EMBASE, CINAHL, PsychINFO, and AMED were searched from inception to 7th June 2016. Selection criteria: Intervention and observational studies investigating the effects of free-living PA on balance in healthy community-dwelling adults (50 years and older). Data extraction and analysis: Thirty studies were eligible for inclusion. Data extraction and risk of bias assessment were independently carried out by two review authors. Due to the variety of outcome measures used in studies, balance outcomes from observational studies were pooled as standardised mean differences or mean difference where appropriate and 95% confidence intervals, and outcomes from RCTs were synthesised using a best evidence approach. Results Limited evidence provided by a small number of RCTs, and evidence from observational studies of moderate methodological quality, suggest that free-living PA of between one and 21 years’ duration improves measures of balance in older healthy community-dwelling adults. Statistical analysis of observational studies found significant effects in favour of more active groups for neuromuscular measures such as gait speed; functionality using Timed Up and Go, Single Leg Stance, and Activities of Balance Confidence Scale; flexibility using the forward reach test; and strength using the isometric knee extension test and ultrasound. A significant effect was also observed for less active groups on a single sensory measure of balance, the knee joint repositioning test. Conclusion There is some evidence that free-living PA is effective in improving balance outcomes in older healthy adults, but future research should include higher quality studies that focus on a consensus of balance measures that are clinically relevant and explore the effects of free-living PA on balance over the longer-term

Girls and Boys Born before 28 Weeks Gestation: Risks of Cognitive, Behavioral, and Neurologic Outcomes at Age 10 Years

To compare the prevalence of cognitive, neurological, and behavioral outcomes at 10 years of age in 428 girls and 446 boys who were born extremely preterm (EP)

The Relationship of Maternal Prepregnancy Body Mass Index and Pregnancy Weight Gain to Neurocognitive Function at Age 10 Years among Children Born Extremely Preterm

OBJECTIVE: To assess the association between maternal prepregnancy body mass index and adequacy of pregnancy weight gain in relation to neurocognitive function in school-aged children born extremely preterm. STUDY DESIGN: Study participants were 535 ten-year-old children enrolled previously in the prospective multicenter Extremely Low Gestational Age Newborns cohort study who were products of singleton pregnancies. Soon after delivery, mothers provided information about prepregnancy weight. Prepregnancy body mass index and adequacy of weight gain were characterized based on this information. Children underwent a neurocognitive evaluation at 10 years of age. RESULTS: Maternal prepregnancy obesity was associated with increased odds of a lower score for Differential Ability Scales-II Verbal IQ, for Developmental Neuropsychological Assessment-II measures of processing speed and visual fine motor control, and for Wechsler Individual Achievement Test-III Spelling. Children born to mothers who gained an excessive amount of weight were at increased odds of a low score on the Oral and Written Language Scales Oral Expression assessment. Conversely, children whose mother did not gain an adequate amount of weight were at increased odds of a lower score on the Oral and Written Language Scales Oral Expression and Wechsler Individual Achievement Test-III Word Reading assessments. CONCLUSION: In this cohort of infants born extremely preterm, maternal obesity was associated with poorer performance on some assessments of neurocognitive function. Our findings are consistent with the observational and experimental literature and suggest that opportunities may exist to mitigate risk through education and behavioral intervention before pregnancy

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology